A p300 and SIRT1 Regulated Acetylation Switch of C/EBPα Controls Mitochondrial Function.

Autor:	Zaini MA; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Leibniz Institute on Aging, Fritz Lipmann Institute, 07745 Jena, Germany., Müller C; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands., de Jong TV; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands., Ackermann T; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands., Hartleben G; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands., Kortman G; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands., Gührs KH; Leibniz Institute on Aging, Fritz Lipmann Institute, 07745 Jena, Germany., Fusetti F; Department of Biochemistry, Netherlands Proteomics Centre, Groningen Biological Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, the Netherlands., Krämer OH; Institute of Toxicology, University Medical Center Mainz, 55131 Mainz, Germany., Guryev V; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands., Calkhoven CF; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands. Electronic address: c.f.calkhoven@umcg.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Jan 09; Vol. 22 (2), pp. 497-511.
DOI:	10.1016/j.celrep.2017.12.061
Abstrakt:	Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic pathways in response to changes in nutrient supply. Among the transcription factors that regulate gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other physiological processes. Here, we show that C/EBPα is acetylated by the lysine acetyl transferase (KAT) p300 and deacetylated by the lysine deacetylase (KDAC) sirtuin1 (SIRT1). SIRT1 is activated in times of energy demand by high levels of nicotinamide adenine dinucleotide (NAD + ) and controls mitochondrial biogenesis and function. A hypoacetylated mutant of C/EBPα induces the transcription of mitochondrial genes and results in increased mitochondrial respiration. Our study identifies C/EBPα as a key mediator of SIRT1-controlled adaption of energy homeostasis to changes in nutrient supply. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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